The GPR88 Agonist RTI‐122 Reduces Alcohol‐Related Motivation and Consumption
PMCID: PMC12178211
PMID: 40536830
DOI: 10.1111/adb.70058
Journal: Addiction biology
Publication Date: 2025-6-19
Authors: Lovelock DF, Liu W, Hamida SB, Cordero VL, Van Voorhies KJ, et al.
Key Points
- RTI-122 demonstrates a selective, receptor-specific mechanism for reducing alcohol consumption across multiple experimental models
- Significant reductions in alcohol intake observed at 5-10 mg/kg doses, with dose-dependent effects varying between male and female subjects
- Potential novel pharmacological approach targeting GPR88 receptor for AUD treatment, with specificity for alcohol reward circuits
Summary
This preclinical study investigated RTI-122, a GPR88 receptor agonist, as a potential therapeutic intervention for alcohol use disorder (AUD). By systematically examining alcohol consumption and motivation across multiple experimental paradigms in mice and rats, researchers demonstrated that RTI-122 selectively reduces alcohol intake without affecting general reward mechanisms or water consumption.
The study revealed dose-dependent effects of RTI-122 in reducing alcohol self-administration, motivation to consume alcohol, and stress-induced reinstatement of alcohol-seeking behavior. Critically, these effects were GPR88 receptor-specific, confirmed by knockout studies showing no reduction in alcohol intake in Gpr88 knockout mice. The compound's efficacy was consistent across different experimental conditions, including two-bottle choice tests, operant self-administration, and progressive ratio tasks, suggesting a robust mechanism for potentially treating AUD.